This invention relates to novel purified forms of a protein found in cells infected with human T-cell lymphotrophic virus III (HTLV-III) and related viruses; the invention also relates to polypeptides, kits, and assays for detecting in a biological specimen the presence of that protein's antigenic determinants or of antibodies to one or more such antigenic determinants. For convenience, the term "HTLV-III related viruses" is used in this application to include viruses that are closely related to HTLV-III by serological biochemical and molecular criteria, including lymphadenopathy associated virus (LAV) (see Barre-Sinoussi (1983) Science 220:859), ARV (see Sanchez-Pescador (1985) Science 227:484) and AAV, and other forms, subtypes and variants, including simian viruses. The terms "human T-cell lymphotrophic virus" and "human T-cell leukemia virus" are used interchangeably, although the former is preferable.
Human T-cell lymphotrophic virus III (HTLV-III) is believed to play a key role in the pathogenesis of acquired immunodeficiency syndrome (AIDS). It has been shown that human patients whose bodies contain antibodies to HTLV-III-infected cells are apparently latently or actively infected with the virus. There are various tests to determine the presence of antibodies to HTLV-III proteins in a biological specimen. For example, an ELISA test is widely used for blood bank screening. For such assays, the goal is to screen out all individuals who have been exposed to HTLV-III, whether or not such individuals have developed or will develop AIDS.
Other HTLV-III-encoded polypeptides that are antigenic when expressed in infected individuals include:
1) a 55 kd gag polyprotein (p55) which yields a 24 kd protein (p24) as the major virus core protein and a 17 kd phosphoprotein (pp17) (Schupbach et al. (1984) Science 224:503-505); and
2) a gp160 env polyprotein which gives rise to gp120 at the amino terminus (see Essex and Lee, U.S. Ser. No. 670,361, filed Nov. 9, 1984, which is hereby incorporated by reference).
The disease course for patients who exhibit HTLV-III antibodies varies; some such patients are healthy and currently uninfected, others harbor the virus with few symptoms, still others have chronic symptoms that have been designated "AIDS related complex" (ARC), and, finally, some such individuals are AIDS patients, exhibiting immunodeficiencies that are ultimately fatal. It also appears that some ARC or non-symptomatic patients harboring the virus may develop AIDS after prolonged periods.